Effect of the Memory Training for Recovery–Adolescent Intervention vs Treatment as Usual on Psychiatric Symptoms Among Adolescent Girls in Afghanistan

Key Points Question Can Memory Training for Recovery–Adolescent (METRA) improve psychiatric symptoms among adolescent girls affected by war in Afghanistan? Findings In this randomized clinical trial of 125 adolescent girls with heightened psychiatric distress, those who received METRA had significantly greater reductions in posttraumatic stress disorder and depression symptoms than those allocated to treatment as usual, and these improvements were maintained at the 3-month follow-up. Meaning The findings indicate that METRA is an effective, feasible, and acceptable treatment for symptoms of posttraumatic stress disorder and depression in adolescent girls affected by war in Afghanistan.

(150 per site). Exclusion Criteria: a) high levels of suicidality, b) unmanaged psychosis/manic episodes in past month, and c) presence of head trauma/organic brain damage.

Who will take informed consent? {26a}
Researchers will gain informed consent from the adolescents and their guardians. Treatment as usual (TAU): Local NGOs will provide the course of intervention that they deem appropriate. No specific instructions will be given as to what TAU should entail, except not including elements specific to METRA. TAU will be documented ensuring understanding of the duration, frequency and type of treatment administered.
Participants practice recalling memories in response to positive and neutral cues, with support from the group facilitator. Attention is paid to the contextual, spatio-temporal and sensory-perceptual details of the memories (Raes et al., 2009). Participants' responses are discussed in the group. At the end of the session, homework exercises are introduced; for 10 cues (positive and neutral) participants need to generate a specific memory and are instructed to write down a 'specific memory of the day' every evening of the coming week (Raes et al., 2009). Session 2 starts with a brief summary of Session 1, the homework exercises are discussed and the Session then follows the same format as Session 1, with further practice focusing on recalling memories in response to positive and neutral cues. At the end of Session 2, the homework is explained; participants need to generate two different specific memories for 10 cues (positive and neutral) and write down two different 'specific memories of the day' every evening of the coming week (Raes et al., 2009).
Session 3 is very similar to Session 2. However, in Session 3, participants also need to work with negative cues. The homework exercises are similar to those outlined in Session 2, but now also include negative cues. Session 4 involves further exercises using negative and ('counterpart') positive cues. It is also explained how overgeneral thinking can be addressed by recalling a single specific experience and examples are discussed to promote metacognitive awareness of when participants are starting to shift to unspecific thinking or more general retrieval (Raes et al., 2009).
Session 5 includes further practice and a summary of Module 1. Module 1 focuses on everyday remembering.
Module 2: Writing for Recovery is a written exposure training involves five sessions (Kalantari et al., 2012;Sloan et al., 2018). In the first session the purpose of Module 2 is outlined. In the following sessions, the facilitator simply reads the instructions and the participant completes the writing task; writing about their trauma including thoughts and feelings. After 30 minutes, the facilitator instructs the participants to stop writing.

Criteria for discontinuing or modifying allocated interventions {11b}
Discontinue trial if participants report significant distress or a significant proportion of participants report significant increase in symptomatology. This will be based on the reports and observations of the facilitators and decisions to continue/discontinue will be made by the trial monitoring body.

Sample size {14}
A priori power analysis was undertaken using G*Power for depression and PTSD outcomes to detect a small to moderate interaction effect (f=0.15) [18,33] between group (intervention, control) and time (pre-test, posttest) at an alpha-level of 0.05. A sample size of 90 participants would achieve power >0.80. The sample size estimate was re-adjusted to allow for attrition and we aim to recruit >100 participants in both sites (Kabul and Herat).

Recruitment {15}
Participants will be recruited through local non-government agencies and schools in Herat and Kabul. Personal information about potential and enrolled participants will only be collected, shared, maintained and monitored by the research teams at each site. De-identified data will be shared between the team.

Assignment of interventions: allocation
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

Statistical methods
Statistical methods for primary and secondary outcomes {20a} All primary analyses will be on intent-to-treat principle, with all randomized participants analyzed in their allocation condition.
Objective 1 will be examined using linear mixed effects models with intervention type, time, and intervention by time interaction as fixed factors. Repeated assessments of individuals will be modelled as random intercept. Of primary interest will be the intervention by time interaction, which will compare the levels of change over time in outcomes of the METRA and TAU groups.
Between-condition effect sizes (Cohen d) will be calculated and interpreted using guidelines from Cohen. Levels of significance will be set at α<.05 and hypothesis tests will be 2-sided.. Our primary analysis will use data from both sites. Supplementary analyses include separate analyses being conducted for each site. Objective 2: Thematic analysis of qualitative data (Atkins et al., 2017;Braun & Clark, 2006;Marks & Yardley, 2004) will assess feasibility and appropriateness.
Objective 3: Mediational analyses will be carried out using regression-based approach outlined by McKinnon et al. (2007). This will assess mechanisms of change (memory specificity, rumination, avoidance).
Objective 4: We will look at the difference in outcomes and costs between METRA and TAU, allowing us to explore the cost per point change in symptoms for both. Difference in outcomes will be assessed by examining point changes in PTSD and depression symptoms based on our outcome scales. For costs, we will use bottom-up costing of both METRA and TAU whereby we identify the costs of all inputs (e.g., staff time: X minutes at $X salary per minute, X rooms at $X per room, exclusive of research-related costs) and sum them. We can then divide total costs by total point changes for each intervention and compare them. We will also compare total and per patient METRA program costs with existing mental health budgets in humanitarian contexts to give an indication of whether implementing METRA can be affordable in humanitarian settings.

Methods for additional analyses (e.g. subgroup analyses) {20b}
Exploratory Analyses: Potential moderators (age, gender, trauma exposure, location, refugee experience) of intervention response will be explored with linear mixed models.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

N/A
Plans to give access to the full protocol, participant level-data and statistical code {31c}

Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d} The Trial Steering Committee will provide overall supervision of the project. It will include independent members who will monitor trial progress, functioning of the partnership and ensure local and community involvement.
Composition of the data monitoring committee, its role and reporting structure {21a} Not applicable

Adverse event reporting and harms {22}
Should an adverse effect be reported, the Chief Investigators will be notified immediately and a plan to resolve the serious adverse effect will be formulated. Depending on the nature of the adverse event, the Chief Investigators and research team will determine the appropriate course of action and then the research team will discuss the situation fully with the participant. A complete list of adverse effects, the steps taken to resolve them, and the results of those steps, will be reported to the Ethics Review Committee, Trial Steering Committee, Kabul University and Behrawan monthly, while serious adverse effects will be reported within one business day.

Frequency and plans for auditing trial conduct {23}
The Trial Steering Committee will provide overall supervision of the project.
Plans for communicating important protocol amendments to relevant parties (e.g. trial

participants, ethical committees) {25}
We will report changes to the ethic committees and trial registry.

Dissemination plans {31a}
The results will be published in peer-reviewed journal articles. There will also be an Engagement and Communication Strategy that will ensure key local (Afghanistan) and international stakeholders are informed about the findings.

Discussion
The complex humanitarian context of Herat and Kabul present operational challenges, as several of the universities are in the process of re-establishing themselves. However, our collaborations are well-established and we will follow the research protocols that were employed in our pilot work in this region.

Trial status
Protocol version number 1; July 2021.

Availability of data and materials {29}
The research team will have the final dataset and this dataset will be available by contacting the In order to meet these identified needs, we propose that MEmory Training for Recovery-Adolescent (METRA), a low-intensity, accessible and scalable evidence-based intervention, will improve adolescent mental health (specifically depression and PTSD), .

Trauma and Memory
Those suffering from depression and PTSD, including adolescent refugees and war-affected youth , exhibit certain disruptions in their autobiographical remembering (i.e., remembering personal experiences from one's life) (Brewin, 2011;Dalgleish & Werner-Seidler, 2014). Trauma memories are often intrusive and distressing (Brewin, 2011) and PTSD sufferers have considerable difficulties remembering specific events from their lives (e.g., "I attended Adina's party on Friday"). Instead, they provide overgeneral memories (OGM) of events ("I was attending a party every weekend") (Williams et al., 2007). OGM develops as a cognitive avoidance strategy in response to the distressing memories one may experience (Williams et al., 2007).
OGM is problematic as it is associated with impaired social problem-solving, cognitive avoidance, rumination, impairments in executive control, difficulty imagining specific events in the future (Kleim, Graham, Fihosy, Stott, & Ehlers, 2014;Sutherland & Bryant, 2008;Williams et al., 2007), and difficulty accessing specific information about the past, which interferes with the ability to update distressing memories (Moradi, Moshirpanahi, Parhon, Mirzaei, Dalgleish, & Jobson, 2014;Williams et al., 2007). Each of these processes are integral to recovery from PTSD and depression (Moradi et al., 2014;. Not surprisingly, an OGM retrieval style in adolescents has been found to predict on-going psychological difficulties, which can persist well into adulthood affecting social functioning and academic/vocational attainment (Hitchcock, Nixon, & Weber, 2014).
There is enormous untapped potential to improve the psychological functioning of refugee and waraffected adolescents by targeting these memory difficulties that underpin posttraumatic psychological distress. In response to this, we propose that MEmory Training for Recovery-Adolescents (METRA), a novel intervention for use in humanitarian contexts (Moradi et al., 2014;, may have potential in improving the psychological adjustment of adolescents.

Feasibility and Piloting of METRA Modules
METRA is an evidence-based, low-intensity, easily disseminable, transdiagnostic training package.
It is comprised of two modules that target major cognitive features underpinning posttrauma psychological difficulties experienced by adolescent refugees; OGM and trauma/distressing memories.
METRA, a low-intensity intervention, seems feasible in humanitarian settings and has potential for reducing PTSD and depression symptoms in refugee adolescents. There is a need to better understand the mechanisms driving the therapeutic effects of METRA and the costs associated with implementing METRA in humanitarian contexts. This project addresses identified humanitarian mental health research gaps (Elrha, 2015) by investigating the efficacy and feasibility of scaling-up a low-intensity modular transdiagnostic psychosocial interventions for adolescents. It also includes qualitative methods to examine appropriateness and acceptability of METRA and a healtheconomic component to undertake cost-analysis of the intervention.

Objectives {7}
Primary Objectives 1) Investigate the efficacy of METRA in improving psychological symptoms (posttraumatic stress disorder, depression) in adolescents living in refugee-like and humanitarian situations.

Secondary Objectives
2) Investigate the feasibility and appropriateness of METRA for adolescents living in refugee-like and humanitarian situations delivered in LMIC humanitarian contexts.

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3) Examine the mechanisms mediating treatment effects.

Trial design {8}
This is a randomised controlled trial (RCT) comparing METRA to treatment as usual (TAU), with an embedded qualitative component. Participants will be assessed; 1) at baseline, 2) at post-Module 1, 3) at post-Module 2, and 4) at 6-month 3-month follow-up (CHANGE 2: Follow-up was changed to 3-months. This decision was made due to security issues and increased movement within Afghanistan following the change in government). The first three assessments are face-to-face assessment and will include all measures. The follow-up assessments will be conducted by phone/skype/zoom and will include the primary and secondary outcomes. Assessments will be conducted by independent raters who have no therapeutic relationship with participants and are blind to condition.

Study setting {9}
The Afghan humanitarian crisis has been identified as one of the world's most complex, severe and protracted humanitarian emergencies, with no sign of abatement (UNHCR, 2017 participants need to generate a specific memory and are instructed to write down a 'specific memory of the day' every evening of the coming week (Raes et al., 2009). Session 2 starts with a brief summary of Session 1, the homework exercises are discussed and the Session then follows the same format as Session 1, with further practice focusing on recalling memories in response to positive and neutral cues. At the end of Session 2, the homework is explained; participants need to generate two different specific memories for 10 cues (positive and neutral) and write down two different 'specific memories of the day' every evening of the coming week (Raes et al., 2009).
Session 3 is very similar to Session 2. However, in Session 3, participants also need to work with negative cues. The homework exercises are similar to those outlined in Session 2, but now also include negative cues. Session 4 involves further exercises using negative and ('counterpart') positive cues. It is also explained how overgeneral thinking can be addressed by recalling a single specific experience and examples are discussed to promote metacognitive awareness of when participants are starting to shift to unspecific thinking or more general retrieval (Raes et al., 2009).
Session 5 includes further practice and a summary of Module 1. Module 1 focuses on everyday remembering.
Module 2: Writing for Recovery is a written exposure training involves five sessions (Kalantari et al., 2012;Sloan et al., 2018). In the first session the purpose of Module 2 is outlined. In the following sessions, the facilitator simply reads the instructions and the participant completes the writing task; writing about their trauma including thoughts and feelings. After 30 minutes, the facilitator instructs the participants to stop writing (CHANGE 4: Timing of sessions reduced due to

Sample size {14}
A priori power analysis was undertaken using G*Power for depression and PTSD outcomes to detect a small to moderate interaction effect (f=0.15) [18,33] between group (intervention, control) and time (pre-test, posttest) at an alpha-level of 0.05. A sample size of 90 participants would achieve power >0.80. The sample size estimate was re-adjusted to allow for attrition and we aim to recruit >100 participants.

Recruitment {15}
Participants will be recruited through local non-government agencies and schools in Herat and Kabul.

Availability of data and materials {29}
The research team will have the final dataset and this dataset will be available by contacting the researchers.
Ethics approval and consent to participate {24}